RhoJ defines angiogenic endothelial cell motility by integrating VEGF and Sema3E signals

概要

論文の詳細を見る
During tissue morphogenesis, cells migrate in response to diverse extrinsic cues. For angiogenic endothelial cells (ECs), vascular endothelial growth factor (VEGF) and semaphorin 3E (Sema3E) are a pivotal attractant and repellent, respectively. However, it is still unclear how individual ECs integrate these opposite signals to determine their migratory behaviors. Here, we show that the small GTPase RhoJ is an EC-intrinsic integrator of VEGF and Sema3E signals. In its GTP-bound state, RhoJ bound to the cytoplasmic domain of PlexinD1. Upon Sema3E stimulation, RhoJ was released from PlexinD1 and directly induced cell contraction. Upon VEGF stimulation, RhoJ facilitated VEGFR2-PlexinD1 association, thereby preventing VEGFR2 degradation, prolonging downstream signal transduction events, and promoting directional EC movements. Consequently, RhoJ deficiency, even in a single allele, led to variable morphogenetic defects in retinal vascular patterning. Our results indicate that RhoJ may be a novel therapeutic target to manipulate EC motility in disease or tissue regeneration.
日本微小循環学会の論文